Clinical features of subungual melanoma according to the extent of Hutchinson's nail sign: a retrospective single-centre study.

BACKGROUND: Hutchinson's nail sign (HS) is among the diagnostic criteria for subungual melanoma (SUM). However, there is minimal evidence supporting the overall clinical significance of HS in SUM. OBJECTIVES: To identify clinicopathological features of SUM according to the extent of HS. METHODS: Retrospective cohort study was performed with consecutive SUM patients at a single centre from January 2006 to December 2017. The extent of HS was defined by the number of affected nail folds (range 0-4). Comparison groups were organized as follows: patients with HS (affecting ≥1 nail folds) vs. without HS; patients with HS affecting ≥2 nail folds vs. HS affecting <2 nail folds; patients with HS affecting ≥3 nail folds vs. HS affecting <3 nail folds. Clinicopathological characteristics of SUM were compared between the groups. RESULTS: Sixty-one SUM patients were included. Forty-six (75.4%) exhibited HS; 22 (47.8%) on a toe and 24 (52.2%) on a finger. In multivariate analysis, nail destruction [hazard ratio (HR), 10.00; 95% confidence interval (CI), 2.61-38.30; P = 0.001] was significantly associated with the presence of HS and amputation was significantly associated with HS affecting ≥2 nail folds (HR, 4.75; 95% CI, 1.36-16.61; P = 0.015). High T stage (HR, 1.85; 95% CI, 1.20-2.85; P = 0.005, Fig. 2) was significantly associated with HS appearing in ≥3 nail folds. CONCLUSION: Besides its value of detecting SUM, HS provides useful clinical information. The number of nail folds exhibiting HS could be a useful clinical clue for planning therapeutic strategies for SUM.

Lactococcus lactis KR-050L extract suppresses house dust mite induced-atopic skin inflammation through inhibition of keratinocyte and mast cell activation.

AIMS: Atopic dermatitis (AD) is a chronic inflammatory skin disease, with a steadily increasing prevalence. Lactic acid bacteria (LAB) have been widely used in the food industry and are an attractive option for preventing and treating allergic skin diseases. We previously isolated new LABs including Lactococcus lactis KR-050L from Gajuknamu kimchi, and showed the anti-inflammatory effects of extract of L. lactis KR-050L culture broth (LLK). In this study, we investigated the effects of LLK on AD. METHODS AND RESULTS: For the in vitro study, we used human keratinocytes (HaCaT) and mast cells (RBL-2H3). In vivo study, we investigated the effects of LLK on Dermatophagoides farinae extract (DFE) and 2,4-dinitrochlorobenzene (DNCB)-induced atopic skin inflammation in mice. LLK suppressed expression of pro-inflammatory cytokines and chemokines by down-regulation of p38 MAPK, STAT1 and nuclear translocation of NF-κB in keratinocytes. Topical application of LLK suppressed AD symptoms based on reduction in ear thickness, serum IgE levels and immune cell infiltration. Furthermore, LLK inhibited serum histamine levels and mast cells infiltration in vivo, and reduced mast cells activation in vitro. CONCLUSIONS: These results suggest that LLK inhibits AD symptoms through inhibition of keratinocytes and mast cells activation. SIGNIFICANCE AND IMPACT OF THE STUDY: LLK is a potential therapeutic candidate for AD treatment.

Serial sections of atrophic acne scars help in the interpretation of microscopic findings and the selection of good therapeutic modalities.

BACKGROUND: Acne scar causes problems cosmetically and psychologically. Although microscopic examination of acne scars is a necessity for understanding and treatment of them, and it is not easy to find a paper reporting the microscopic characterization of acne scars. OBJECTIVE: The aim of this study was to examine the microscopic findings of acne scars and to select a good therapeutic modality based on the findings. METHODS: Thirty-one atrophic scars obtained from five patients for cosmesis and 18 serial sections were made from each atrophic scar. The sections were stained with H&E, Masson-trichrome or Verhoeff van Gieson stains. Immunohistochemistry was done with antibodies against transforming growth factor-ß, metalloproteinase-1 (MMP-1), MMP-2, MMP-9 and MMP-13. The stained sections were examined under the microscope. RESULTS: The epidermis of the acne scar was characterized by keratin plugging in the hair follicle orifice (32%) and multi-channelled tracts (29%). The dermis of the acne scar had characteristics including a decrease in the dermal thickness and loss of pilosebaceous units. In addition, inflammatory cell infiltrates were seen in the dermis (77%), and insufficient dense collagen fibre deposition was found in the whole dermis (29%). Other findings such as calcium deposition and foreign body reaction were discovered. CONCLUSION: We have found the characteristics of acne scar through the serial sections of several atrophic scars, and suggest that the treatment must reflect several considerations, including the understanding of histopathological findings and the use of combination therapy.

OsCM regulates rice defence system in response to UV light supplemented with drought stress.

Studies on plant responses to combined abiotic stresses are very limited, especially in major crop plants. The current study evaluated the response of chorismate mutase overexpressor (OxCM) rice line to combined UV light and drought stress. The experiments were conducted in pots in a growth chamber, and data were assessed for gene expression, antioxidant and hormone regulation, flavonoid accumulation, phenotypic variation, and amino acid accumulation. Wild-type (WT) rice had reduced the growth and vigour, while transgenic rice maintained growth and vigour under combined UV light and drought stress. ROS and lipid peroxidation analysis revealed that chorismate mutase (OsCM) reduced oxidative stress mediated by ROS scavenging and reduced lipid peroxidation. The combined stresses reduced biosynthesis of total flavonoids, kaempferol and quercetin in WT plants, but increased significantly in plants with OxCM. Phytohormone analysis showed that SA was reduced by 50% in WT and 73% in transgenic plants, while ABA was reduced by 22% in WT plants but increased to 129% in transgenic plants. Expression of chorismate mutase regulates phenylalanine biosynthesis, UV light and drought stress-responsive genes, e.g., phenylalanine ammonia lyase (OsPAL), dehydrin (OsDHN), dehydration-responsive element-binding (OsDREB), ras-related protein 7 (OsRab7), ultraviolet-B resistance 8 (OsUVR8), WRKY transcription factor 89 (OsWRKY89) and tryptophan synthase alpha chain (OsTSA). Moreover, OsCM also increases accumulation of free amino acids (aspartic acid, glutamic acid, leucine, tyrosine, phenylalanine and proline) and sodium (Na), potassium (K), and calcium (Ca) ions in response to the combined stresses. Together, these results suggest that chorismate mutase expression induces physiological, biochemical and molecular changes that enhance rice tolerance to combined UV light and drought stresses.

Immunohistochemical expression of matrix metalloproteinases in the granulomatous rosacea compared with the non-granulomatous rosacea.

BACKGROUND: There is a granulomatous variant which is recognized in the rosacea spectrum. However, the pathogenesis of granuloma formation in rosacea has not been clearly demonstrated. Matrix metalloproteinases (MMPs) are required for recruitment of inflammatory cells and for tissue remodelling, making way for the development of well-organized granuloma. OBJECTIVE: The aim of this study was to investigate the expression of transforming growth factor (TGF)-ß, TGF-ß type II receptor (TßRII), Tumour necrosis factor (TNF)-α, MMP-1, 2 and 9 in the granulomatous rosacea (GR) compared with the non-granulomatous rosacea (NGR) and test the hypothesis that the changes of these profiles in GR would be related with chronic ultraviolet radiation (UVR)-exposure. METHODS: Facial skin samples were obtained from 20 patients with GR and NGR (control group). The sections were stained using haematoxylin and eosin, Verhoeff's elastic stain, and antibodies to TGF-ß, TßRII, TNF-α, MMP-1, -2 and -9. RESULTS: The amount of elastotic material was significantly increased in the dermis of GR lesions. Expression of TGF-ß was significantly decreased in the epidermis of GR lesions compared with NGR lesions. In addition, the expression of MMP-9 was significantly increased in the dermis of GR lesions compared with NGR lesions, especially at the centre of the granuloma on a semi-quantitative analysis. MMP-2 expression was also increased in GR lesions, although the difference between the two groups was not statistically significant. CONCLUSIONS: The results of this study suggest that the increased expression of MMPs in the dermis may participate in granuloma formation of GR in association with UVR.

Prevalence of yeast-like fungi and evaluation of several virulence factors from feral pigeons in Seoul, Korea.

AIMS: Studies of pigeon-borne yeasts have tended to focus on species, such as Cryptococcus neoformans and Candida albicans, with scant attention to feral pigeons in Korea. We studied the prevalence of yeasts from faecal samples of feral pigeons obtained in various public places in Seoul, Korea, and assessed their potential capacity as human pathogens. METHODS AND RESULTS: Three hundred and six pigeon faeces samples were collected at city squares and parks in 21 localities in Seoul and Seoul Grand Park and analysed for yeast with conventional methods. Of the 306 samples, 126 (41·2%) were positive for yeast. Seventeen species of yeast were identified. The most frequent species were Candida glabrata (34·1%), Candida famata (12·7%), Cryptococcus albidus (14·3%) and Cryptococcus laurentii (7·9%). The yeast isolates were tested for virulence. Of the 116 isolates (ten isolates missing), 70·7% (n = 82) grew at 37°C. All the Cryptococcus spp. isolates possessed a capsule, 16·4% (n = 19) produced melanin, and 33·6% (n = 39) produced proteinase. Two Ca. glabrata, a Ca. famata and Ca. albicans as well as three C. neoformans, a C. laurentii and Ca. albicans isolates had three virulence factors. Accordingly, 29·3% (n = 34) isolates possessed more than two virulence factors except capsule formation. CONCLUSIONS: These results of this study indicate that feral pigeons harbour a variety of yeasts and are a reservoir of human pathogenic fungi. SIGNIFICANCE AND IMPACT OF THE STUDY: This study is the first time about the microflora (fungi) presents in faecal samples collected from a variety of public areas throughout Seoul, Korea.

Ultrasonographic evaluation of the femoral vein in anaesthetised infants and young children.

We investigated the cross-sectional area of the femoral vein and its relationship to the femoral artery at two anatomical levels, in infants and children. Sixty-six subjects were allocated to one of two groups: infants (< 1 year, n = 31) or children (1-6 years, n = 35). After induction of general anaesthesia, the femoral vein was evaluated by ultrasound with the patients' legs at 30° and 60° of abduction and their hips externally rotated. In each position, measurements were taken at the level of the inguinal crease and 1 cm below the crease. Hip rotation with 60° leg abduction decreased femoral artery overlap at the level of the inguinal crease in both infants (p = 0.013) and children (p = 0.003). Thus, the optimal place for femoral vein cannulation in paediatric patients seems to be at the level of the inguinal crease with 60° leg abduction and external hip rotation.

Oestrogen and progesterone receptor expression in melasma: an immunohistochemical analysis.

BACKGROUND: Melasma is a commonly acquired symmetrical hypermelanosis on sun-exposed areas of the skin. The development of melasma appears to be associated with increased levels of oestrogen, exposure to sunlight and a genetic predisposition. Several in vitro studies have partially clarified the effects of oestrogen and progesterone on melasma. However, oestrogen receptor (ER) and progesterone receptor (PR) expression in melasma-affected skin has not been investigated to date, except for one case report on ER expression. OBJECTIVE: The purpose of this study was to compare ER and PR expression between hyperpigmented areas and unaffected areas of facial skin in patients with melasma. METHODS: Biopsies were performed on skin lesions and adjacent-unaffected facial skin in 33 Korean women with melasma. The sections were stained using haematoxylin and eosin, Fontana-Masson, and antibodies to NKI/beteb, ERα, ß and PR. RESULTS: The immunohistochemical expression of ERß showed an increasing tendency in epidermal lesions without statistical significance. Expression of PR was significantly increased in the epidermal lesions compared with unaffected skin on the computer-assisted image analysis. Interestingly, there was increased ERß expression in the dermal lesions especially around small blood vessels and fibroblast-like cells compared with unaffected dermis on the semi-quantitative analysis. However, there was no significant difference in the expression of PR between the dermal lesions and unaffected dermis. CONCLUSION: The results of this study may provide useful information for further investigation into the pathogenesis and therapeutic approaches for treating melasma in relation to hormonal factors. The role of ER in the dermis in association with dermal environment such as blood vessels and fibroblasts remains to be further clarified.

Cleavage of phospholipase D1 by caspase promotes apoptosis via modulation of the p53-dependent cell death pathway.

The enzymatic activity of phospholipase D (PLD) is known to be essential for cell survival and protection from apoptosis. However, the mechanisms regulating PLD activity during apoptosis remain unknown. Here we report that cleavage of PLD1 by caspases facilitates p53-mediated apoptosis. Cleavage of PLD1 into an N-terminal fragment (NF-PLD1) and a C-terminal fragment at the amino-acid sequence, DDVD(545), led to a reduction in PLD1 activity. However, a caspase-resistant mutant form of PLD1 retained significant levels of enzymatic activity and apoptotic function as compared to wild-type PLD1. Exogenous NF-PLD1 expression induced apoptosis through a dominant-negative effect on the activity of endogenous PLD1. During apoptosis, a small fraction of PLD1 is cleaved by caspases in a p53-independent manner and NF-PLD1 amplifies apoptotic signaling through inhibition of the remaining PLD1 activity. As PLD1 suppresses the ATM-Chk2-p53 pathway, elimination of PLD1 activity through NF-PLD1 or si-RNA against PLD1 increases apoptosis in a p53-dependent manner. Taken together, our results reveal that cleavage of PLD1 by caspases promotes apoptosis via modulation of the p53-dependent cell death pathway.

The rate of Salmonella spp. infection in zoo animals at Seoul Grand Park, Korea.

Salmonellosis is an important zoonotic disease that affects both people and animals. The incidence of reptile-associated salmonellosis has increased in Western countries due to the increasing popularity of reptiles as pets. In Korea, where reptiles are not popular as pets, many zoos offer programs in which people have contact with animals, including reptiles. So, we determined the rate of Salmonella spp. infection in animals by taking anal swabs from 294 animals at Seoul Grand Park. Salmonella spp. were isolated from 14 of 46 reptiles (30.4%), 1 of 15 birds (6.7%) and 2 of 233 mammals (0.9%). These findings indicate that vigilance is required for determining the presence of zoonotic pathogen infections in zoo animals and contamination of animal facilities to prevent human infection with zoonotic diseases from zoo facilities and animal exhibitions. In addition, prevention of human infection requires proper education about personal hygiene.

Analytical model development for the prediction of the frictional resistance of a capsule endoscope inside an intestine.

For the purpose of optimizing the design of the locomotion mechanism as well as the body shape of a self-propelled capsule endoscope, an analytical model for the prediction of frictional resistance of the capsule moving inside the small intestine was first developed. The model was developed by considering the contact geometry and viscoelasticity of the intestine, based on the experimental investigations on the material properties of the intestine and the friction of the capsule inside the small intestine. In order to verify the model and to investigate the distributions of various stress components applied to the capsule, finite element (FE) analyses were carried out. The comparison of the frictional resistance between the predicted and the experimental values suggested that the proposed model could predict the frictional force of the capsule with reasonable accuracy. Also, the FE analysis results of various stress components revealed the stress relaxation of the intestine and explained that such stress relaxation characteristics of the intestine resulted in lower frictional force as the speed of the capsule decreased. These results suggested that the frontal shape of the capsule was critical to the design of the capsule with desired frictional performance. It was shown that the proposed model can provide quantitative estimation of the frictional resistance of the capsule under various moving conditions inside the intestine. The model is expected to be useful in the design optimization of the capsule locomotion inside the intestine.

Polyphenol (-)-epigallocatechin gallate protection from ischemia/reperfusion-induced renal injury in normotensive and hypertensive rats.

INTRODUCTION: The effect of epigallocatechin gallate (EGCG) in an in vivo renal model of ischemia with reperfusion (I/R) was compared between normotensive (WKR) and hypertensive (SHR) rats. METHODS: WKR (groups I, II, III) and SHR groups (groups IV, V, VI) were divided into three types. Groups I and IV were sham-operated animals; groups II and V were subjected to 45 minutes of renal I/R; and groups III and VI received 10 mg/kg EGCG intravenously at the time of reperfusion. Three days after renal I/R, we compared renal function markers, malondialdehyde (MDA), and histologic changes. RESULTS: Following renal I/R, levels of blood urea nitrogen (BUN) and serum creatinine (sCr) were increased and serum creatinine clearance (CrCl) decreased in group V compared to group II (P < .001). Those receiving EGCG treatment (groups III and VI) had decreased BUN and sCr compared to non-EGCG I/R groups (P < .001), but not surprisingly, higher than sham groups. CrCl was lowest in the SHR groups. The MDA was significantly decreased after EGCG treatment (P = .028 in group III, P = .002 in group VI). Following renal I/R, tissue necrosis was more severe among SHR (P < .001). However, the ratio of regeneration to damage significantly increased in SHR after EGCG treatment. CONCLUSIONS: The reperfusion injury was greater among SHR compared with WKR in terms of renal function, lipid peroxidation, and tissue damage. EGCG treatment significantly ameliorated renal impairment and promoted tissue regeneration following renal I/R.

Suprascapular neuropathy in massive rotator cuff tears with severe fatty degeneration in the infraspinatus muscle.

AIMS: Our aim was to describe the atypical pattern of increased fatty degeneration in the infraspinatus muscle compared with the supraspinatus in patients with a massive rotator cuff tear. We also wished to describe the nerve conduction and electromyography findings in these patients. PATIENTS AND METHODS: A cohort of patients undergoing surgery for a massive rotator cuff tear was identified and their clinical records obtained. Their MRI images were reviewed to ascertain the degree of retraction of the torn infraspinatus and supraspinatus muscles, and the degree of fatty degeneration in both muscles was recorded. Nerve conduction studies were also performed in those patients who showed more degeneration in the infraspinatus than in the supraspinatus. RESULTS: Out of a total of 396 patients who underwent surgery for a massive rotator cuff tear between 2006 and 2015, 35 who had more severe fatty degeneration in the infraspinatus than in the supraspinatus were identified. There were 13 men and 22 women. Their mean age was 67.2 years (56 to 81). A total of 20 (57%) had grade 4 fatty degeneration as classified by Fuchs et al, in the infraspinatus. Patte grade 3 muscle retraction was seen in 25 patients (71%). In all, eight patients (23%) had abnormal nerve conduction studies. The mean retraction of the infraspinatus was 3.6 cm (2.1 to 4.8) in patients with more severe fatty degeneration in the infraspinatus, versus 3.0 cm (1.7 to 5.5) in those with more severe degeneration in the supraspinatus (p = 0.003). The retraction ratios were 0.98 (0.61 to 1.57) and 0.77 (0.38 to 1.92), respectively (p < 0.001). CONCLUSION: Fatty degeneration affecting the infraspinatus more than the supraspinatus may be, in the context of a massive rotator cuff tear, due to entrapment of the suprascapular nerve at the spinoglenoid notch. Cite this article: Bone Joint J 2016;98-B:1505-9.

Genetic alterations in gallbladder adenoma, dysplasia and carcinoma.

Adenoma and dysplasia in the gallbladder (GB) have been reported as precancerous lesions, but the genetic evidence of this is not clearly defined. The purpose of this study was to analyze the frequencies of K-ras, p53, and p16 gene mutations, of microsatellite instability (MI) and of loss of heterozygosity (LOH) in GB cancer, dysplasia, and adenoma. Tissues from 15 GB cancers, five dysplasias around cancerous tumors, and three adenomas were collected prospectively. The mutation rates of K-ras, p53, and p16 were 20.0, 35.7, and 30.7%, respectively, in GB cancers. However, no mutations were found in dysplasia or adenoma. Reduced staining for p16 was seen in 23% of carcinomas. All of the GB carcinomas and four out of five (80%) of the dysplasias showed LOH in a minimum of one locus, but one out of three (33%) cases of adenoma displayed LOH in only one locus. All of the loci of LOH in the dysplasias, except one, showed the same patterns of allelic loss as the adjacent carcinomas. Only one dysplasia showed multiple MI. In conclusion, multiple LOH may be associated with the development of dysplasia and the malignant transformation of GB carcinoma. Gene alterations of K-ras, p53, and p16 are important steps in the malignant changes of dysplasia. However, MI seems to have only a limited role in GB cancer development.

Adsorption of a mixture of Thiobacillus thiooxidans and Thiobacillus ferrooxidans onto copper-containing furnace dust.

The Langmuir adsorption parameter X(Am) of a mixture of culture of Thiobacillus ferrooxidans and Thiobacillus thiooxidans indicates that these bacteria have preferential and competitive adsorption sites on furnace dust. The constant K(A) of the mixture significantly larger than that of each component, suggesting that a synergistic effect may occur in the binding of these bacteria to the dust.

Factors predicting concurrent cholangiocarcinomas associated with hepatolithiasis.

BACKGROUND/AIMS: Hepatolithiasis is a risk factor for cholangiocarcinoma. However, it is difficult to detect early cholangiocarcinoma that occurs as a complication of hepatolithiasis. To identify the factors, which can be used for predicting cholangiocarcinomas in patients with hepatolithiasis, we compared the clinical characteristics of patients who had cholangiocarcinoma associated with hepatolithiasis with those of patients with hepatolithiasis only. METHODOLOGY: Forty patients with cholangiocarcinoma associated with hepatolithiasis (group HC) and 73 patients with hepatolithiasis only (group H) were randomly selected for this study. Mean tumor size was 6.1 +/- 2.4 cm in diameter. RESULTS: Patients of group HC were older (56.7 +/- 8.9 yr) than those of group H (49.2 +/- 12.9 yr) (p < 0.001). Weight loss was more frequent in group HC (51.5%) than in group H (5.5%) (p < 0.001) and serum alkaline phosphatase levels were higher in group HC (181 +/- 184 IU/L) than in group H (426 +/- 385 IU/L) (p < 0.001). The proportion of the patients who had hepatolithiasis in the right or both lobes of the liver was higher in group HC (72.5%) than in group H (50.6%) (p = 0.024). The optimal cutoff value of serum CEA level for cholangiocarcinoma detection was set at 4.2 ng/mL using ROC cure to give a sensitivity of 67.6% and a specificity of 90.5%. Group HC differed from group H because of its lower rates of both abdominal pain and cholangitis, longer duration of stone history, and lower serum albumin level. Factors that did not predict cholangiocarcinoma included sex ratio, white blood cell count, serum bilirubin level, and hepatic atrophy. CONCLUSIONS: Cholangiocarcinoma should be suspected in patients with hepatolithiasis, especially when, the patient is over 40 years old, has a long history of hepatolithiasis with weight loss, a higher level of serum alkaline phosphatase, a lower level of serum albumin, a serum carcinoembryonic antigen level exceeding 4.2 ng/mL, and hepatolithiasis that is located either in the right or both lobes of the liver.

Phospholipase D-mediated autophagic regulation is a potential target for cancer therapy.

Autophagy is a catabolic process in which cell components are degraded to maintain cellular homeostasis by nutrient limitations. Defects of autophagy are involved in numerous diseases, including cancer. Here, we demonstrate a new role of phospholipase D (PLD) as a regulator of autophagy. PLD inhibition enhances autophagic flux via ATG1 (ULK1), ATG5 and ATG7, which are essential autophagy gene products critical for autophagosome formation. Moreover, PLD suppresses autophagy by differentially modulating phosphorylation of ULK1 mediated by mTOR and adenosine monophosphate-activated protein kinase (AMPK), and by suppressing the interaction of Beclin 1 with vacuolar-sorting protein 34 (Vps34), indicating that PLD coordinates major players of the autophagic pathway, AMPK-mTOR-ULK1 and Vps34/Beclin 1. Ultimately, PLD inhibition significantly sensitized in vitro and in vivo cancer regression via genetic and pharmacological inhibition of autophagy, providing rationale for a new therapeutic approach to enhancing the anticancer efficacy of PLD inhibition. Collectively, we show a novel role for PLD in the molecular machinery regulating autophagy.

Phospholipase D1 regulates autophagic flux and clearance of α-synuclein aggregates.

Many neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, are characterized by abnormal accumulations of aggregated proteins. Brains in these diseases also show accumulation of autophagic vesicles in the neuronal cytoplasm, suggesting impairment of the autophagic process. As autophagy involves de novo membrane production and vesicle fusion, extensive changes in lipid molecules are necessary. However, the involvement of signaling lipid-modifying enzymes in autophagy and their roles in neurodegenerative diseases are not clear. Using specific inhibitor, we show that loss of phospholipase D1 (PLD1) activity resulted in an accumulation of microtubule-associated protein light chain 3 (LC3), p62, and polyubiquitinated proteins, signs representing malfunction in autophagic flux. Fluorescence and electron microscopic analyses demonstrated impaired fusion of autophagosomes with lysosomes, resulting in accumulation of autophagosomes. Within the cells with impaired autophagic flux, α-synuclein aggregates accumulated in autophagosomes. Knockdown of PLD1 expression using small interfering RNA also resulted in impaired autophagic flux and accumulation of α-synuclein aggregates in autophagosomes. Neuronal toxicity caused by α-synuclein accumulation was rescued by overexpression of PLD1; however, expression of activity-deficient mutant, PLD1-KRM, showed reduced rescue effects. Finally, we demonstrated that both PLD activity and expression levels were reduced in brain tissues of dementia with Lewy bodies (DLB) patients, whereas the amounts of α-synuclein and p62 were increased in the same tissue samples. Collectively, these results suggest that insufficient PLD activity, and therefore, the changes in phospholipid compositions within membranes, might be an important contributor to impaired autophagic process and protein accumulation in Lewy body diseases.